Investigation of ademol effect on the exchange of nitrogen monoxide in the brain of rats with traumatic brain injury

S.I. Semenenko, A.I. Semenenko, S.S. Polishchuk, L.А. Vozniuk, О.N. Semenenko


Background. High concentrations of nitric oxide (NO) lead to the progression of cerebral circulation disorders against a background of traumatic brain injury (TBI). One of the leading molecular mechanisms of the neurocytoprotective action of mo­dern pharmacological agents is their corrective effect on NO metabolism. Purpose. To evaluate the effect of ademol compared with amantadine sulfate on the state of the L-arginine/NO system in the brain of TBI rats. Materials and methods. The experiments were performed on male rats. An experimental model of heavy TBI was created using a pneumatic gun. The therapeutic effect of ademol in TBI was evaluated at a dose of 2 mg/kg intravenously twice per day for 8 days. As a drug for the control group 0.9% NaCl at a dose of 2 ml/kg was used, and the comparison drug was amantadine sulfate at a dose of 5 mg/kg. To determine the effectiveness of the study drugs the level of L-arginine and the total activity of NO-synthases were used. Results. A comparative analysis of the efficacy of ademol and amantadine sulfate on the 8th day of observation showed that in the TBI group of animals treated with ademol, L-arginine content in the brain was higher by 112 % (p < 0.05) than in the control group. Under these conditions, the total activity of NO-synthase in the brain was lower by 26.6 % (p < 0.05) compared to untreated TBI animals. However, in animals treated with amantadine sulfate, the level of L-arginine in the brain was 72.0 % higher (p < 0.05) than in the control pathology group. The total activity of NO-synthase in the brain was lower by 15.4 % (p < 0.05). Conclusion. Experimental modelling of traumatic brain injury was accompanied by the development in its structures of perturbations in the L-arginine/NO-synthase system. One of the pathogenic mechanisms of the brain protective effect on TBI is the ability of ademol to prevent depletion of L-arginine amino acid reserves in the damaged brain and hyperactivation of NO-synthase, with ademol exceeding amantadine sulfate (p < 0.05).


traumatic brain injury; brain circulation; L-arginine; NO-synthase


Carney N, Totten AM, O'Reilly C. Guidelines for the Management of Severe Traumatic Brain Injury 4th Edition Reviewed for evidence–based integrity and endorsed by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. September 2016/ for Management of Severe TBI 4th_Edition.pdf.

Majdan M, Plancikova D, Brazinova A еt al. Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health. 2016 Dec;1(2):e76-e83. doi: 10.1016/S2468-2667(16)30017-2.

Abou El Fadl MH, O'Phelan KH. Management of Traumatic Brain Injury: An Update. Neurosurg Clin N Am. 2018;29(2):213–221.

Llompart-Pou JA, Pérez-Bárcena J. Geriatric traumatic brain injury: An old challenge. Med Intensiva. 2019 Jan - Feb;43(1):44-46.

Gardner RC, Dams-O'Connor K, Morrissey MR, Manley GT. Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and Future Directions. J Neurotrauma. 2018 Feb 15. doi: 10.1089/neu.2017.5371.

Semenenko AI. Assessment of the therapeutic effect of 0.9% NaCl solution according to cerebral hemodynamics in rat cerebral ischemia-reperfusion. Journal of Grodno State Medical University. 2014;3(47):49-52.

Hatefi M, Behzadi S, Dastjerdi MM et al. Correlation of Homocysteine with Cerebral Hemodynamic Abnormality, Endothelial Dysfunction Markers, and Cognition Impairment in Patients with Traumatic Brain Injury. World Neurosurg. 2017;97:70–79. doi: 10.1016/j.wneu.2016.09.080.

Semenenko AI, Kobelyatsky YuYu, Kondratsky BO, Semenenko IF. Features of the influence of some infusion solutions on cerebral hemodynamics in acute ischemic stroke. Emergency medicine.2016;4(75):118–121. (In Ukrainian).

Uzan M, Tanriover N, Bozkus H et al. Nitric Oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury: inflammation as a possible cause of elevated no metabolites. Surg Neurol. 2001;56(6):350–356.

Ved R, Zaben M. Biomarkers for traumatic brain injury. J Neurol. 2018;10:855–852.

Gula NM, Kosyakova GV, Berdyshev AG. Influence of N-stearoylethanolamine on NO-synthase pathway of nitric oxide generation in aorta and heart of rats with streptozotocin-induced diabetes. Ukr. biochem. 2007;79(5):153-158.

Lapach SN, Chubenko AB, Babich M. Statistical methods in biomedical research using Excel. K.: MORION, 2000:320.

Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4–9.

Schwarzmaier SM, Terpolilli NA, Dienel A et al. Endothelial nitric oxide synthase mediates arteriolar vasodilatation after traumatic brain injury in mice. J Neurotrauma. 2015;32(10):731–738.

Huang X, Wan D, Lin Y et al. Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury. Yonsei Med J. 2017;58(5):1012–1017.

Copyright (c) 2020 EMERGENCY MEDICINE

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта